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Biomedical subjects

K Finke

Publications and source records attributed to K Finke.

At least 19 recordsLinked to original sources

Induction of growth rate and transcriptional modulation of growth promoters and growth inhibitors in epithelial cells by EBV-LMP1.

LMP1 is a genuine oncogene encoded by the Epstein-Barr virus (EBV). The cellular response to expression of the EBV-encoded gene LMP1 in the epithelial cell line Wish was studied. Cells were stably transfected with pCEP-LMP, an expression vector for LMP1. On transcript level a transient expression of the LMP1-gene with a maximum 2 days post transfection was observed. Six days post transfection the rate of DNA synthesis of LMP1-transfected Wish cells was increased by 80% compared to control cells, after 2 further days the number of cells was increased by 32%. A human cDNA-array was screened with probes from LMP1-transfected and control cells showing induction of transcription for proliferation associated genes and repression for growth suppressor genes.

Cell Division↗

Hemispheric dominance in the processing of J.S. Bach fugues: a transcranial Doppler sonography (TCD) study with musicians.

Although the majority of studies on musical processing in musicians observed a left hemisphere dominance which has usually been explained by a proficient analytical strategy used by these subjects, the findings are still inconsistent. Changes in hemispheric activity induced by listening to music (J. S. Bach fugues) and by recognizing the repetitions of the fugue theme were examined, using the technique of bilateral transcranial Doppler sonography (TCD) of the left and right middle cerebral artery (MCA). Subjects were 32 right-handed musicians, half of whom were members of an orchestra or members of a choir. The fugues were presented in two versions: a-cappella and instrumental. During passive listening to the a-cappella version, a weak left-dominant asymmetry of blood flow acceleration was observed, while there was no hemispheric asymmetry during listening to the instrumental version. During the task of fugue theme recognition, a highly significant asymmetry in favour of the right MCA was observed with both versions. It is concluded that when the processing of complex musical material has to be based on the analysis of melodic contour features and calls for working memory capacities a right hemisphere dominance is observed even in musically sophisticated subjects.

Adult↗

A second trimeric complex containing homologs of the Sec61p complex functions in protein transport across the ER membrane of S. cerevisiae.

Yeast microsomes contain a heptameric Sec complex involved in post-translational protein transport that is composed of a heterotrimeric Sec61p complex and a tetrameric Sec62-Sec63 complex. The trimeric Sec61p complex also exists as a separate entity that probably functions in co-translational protein transport, like its homolog in mammals. We have now discovered in the yeast endoplasmic reticulum membrane a second, structurally related trimeric complex, named Ssh1p complex. It consists of Ssh1p1 (Sec sixty-one homolog 1), a rather distant relative of Sec61p, of Sbh2p, a homolog of the Sbh1p subunit of the Sec61p complex, and of Sss1p, a component common to both trimeric complexes. In contrast to Sec61p, Ssh1p is not essential for cell viability but it is required for normal growth rates. Sbh1p and Sbh2p individually are also not essential, but cells lacking both proteins are impaired in their growth at elevated temperatures and accumulate precursors of secretory proteins; microsomes isolated from these cells also exhibit a reduced rate of post-translational protein transport. Like the Sec61p complex, the Ssh1p complex interacts with membrane-bound ribosomes, but it does not associate with the Sec62-Sec63p complex to form a heptameric Sec complex. We therefore propose that it functions exclusively in the co-translational pathway of protein transport.

Amino Acid Sequence↗

Repression of cyclin D1: a novel function of MYC.

Constitutive expression of human MYC represses mRNA levels of cyclin D1 in proliferating BALB/c-3T3 fibroblasts. We expressed a series of mutant alleles of MYC and found that downregulation of cyclin D1 is distinct from previously described properties of MYC. In particular, we found that association with Max is not required for repression of cyclin D1 by MYC in vivo. Conversely, the integrity of a small amino-terminal region (amino acids 92 to 106) of MYC is critical for repression of cyclin D1 but dispensable for transformation of established RAT1A cells. Runoff transcription assays showed that repression occurs at the level of transcription initiation. We cloned the promoter of the gene for human cyclin D1 and found that it lacks a canonical TATA element. Transcription starts at an initiator element similar to that of the adenovirus major late promoter; this element can be directly bound by USF in vitro. Expression of MYC represses the cyclin D1 promoter via core promoter elements and antagonizes USF-mediated transactivation. Taken together, our data define a new pathway for gene regulation by MYC and show that the cyclin D1 gene is a target gene for repression by MYC.

3T3 Cells↗

Differential modulation of cyclin gene expression by MYC.

We have investigated the effects of deregulated expression of the human c-MYC protooncogene on cyclin gene expression and on the transcription factor E2F. We found that constitutive expression of MYC or activation of conditional MycER chimeras led to higher levels of cyclin A and cyclin E mRNA. Activation of cyclin A expression by MYC led to a growth factor-independent association of cyclin A and cdk2 with the transcription factor E2F and correlated with an increase in E2F transcriptional activity. In contrast, expression of the G1 phase cyclin D1 was strongly reduced in MYC-transformed cells. In synchronized cells, repression of cyclin D1 by MYC occurred very early in the G1 phase of the cell cycle.

3T3 Cells↗

Three years of experience with the swan-neck Tenckhoff catheter.

In a retrospective study over three years, 23 patients were provided with a swan-neck Tenckhoff catheter (SNC) and 49 patients (control group) with a straight Tenckhoff catheter (STC) at the beginning of CAPD and were observed over a follow-up period of 608 patient-months. The aim of the study was to examine the reduction of complications in the course of CAPD with SNC resulting from technical causes, such as catheter dislocations, infections at the catheter's point of exit, the tunnel and the peritoneum. The causes of renal insufficiency, the reasons for choosing CAPD as a dialytic procedure, the causes of catheter loss as well as the frequency of infections associated with CAPD were analyzed. The main reasons for catheter loss were peritonitis and dislocations. In the SNC group a significant reduction of dislocations to 8.7% was observed as against 26.5% with STC. On the other hand, with SNC significantly more cases of peritonitis were observed in terms of statistics, with 1.1 episodes per patient-year (EOP/PY) compared with 0.3 EOP/PY with STC. The frequency of the exit site and tunnel infections and the cumulative survival probability of the catheters did not differ. The SNC is an interesting alternative to the STC; however, the expectations were only partly met.

Catheterization↗

[Mexiletine in terminal renal failure and various dialysis procedures].

We monitored the plasma levels of mexiletine in 20 dialysis patients with severe cardiac arrhythmias after repeated oral administration and the elimination by various dialysis procedures. The levels of mexiletine in plasma and dialysate were assayed by high-pressure liquid chromatography. After repeated administration of mexiletine 400-600 mg/day trough levels were in the range from 500-2,000 ng/ml. Treatment controlled by Holter monitoring was effective in 13/20 patients. Doses of 600 mg/day and more often were not tolerated by patients with dialysis after some weeks. There was no important removal of mexiletine from plasma during hemodialysis, hemofiltration, peritoneal dialysis, or plasmapheresis. In conclusion, we recommend a slightly reduced dosage of 400-600 mg mexiletine/day (usually 600-800 mg) for patients with end-stage renal insufficiency, irrespective of dialysis.

Adult↗

[Angiotensin-converting enzyme and 1,25-dihydroxyvitamin D3 in hypercalcemia of unknown origin].

Sarcoidosis of the kidneys and liver without radiologically demonstrable lung involvement in a 44-year-old woman was shown to be the cause of a hypercalcaemia syndrome. The hypercalcaemia was presumably due to an increased production of 1,25-(OH)2-vitamin D3 which--like the increased angiotensin converting enzyme--is produced in the epithelioid and giant cells. Corticoid treatment normalized serum calcium and ACE levels and improved renal function. These observations demonstrate that measurement of ACE and 1,25-(OH)2-vitamin D3 levels is helpful in the differential diagnosis of hypercalcaemia, in view of the possibility of sarcoidosis, and should be among the diagnostic tests.

Adult↗

Analysis of cardiovascular risk factors in chronic hemodialysis patients with special attention to the hyperlipoproteinemias.

A group of 252 chronic hemodialysis patients was examined for various risk factors. Special emphasis was placed upon the comparison of patients who had marked cardiovascular alterations with the remainder of the group. The seriousness of the risk factors was determine by hypertension and hyperlipoproteinemia, 78% of the patients received antihypertensive medication or had changes in the fundus of the eye or both. In 74% of the patients there were pathological changes in the plasma lipids or lipoproteins or both. Hypertriglyceridemia (49%) and a HDL cholesterol decrease (61%) were the most striking findings. The average VLDL cholesterol value was significantly higher and the HDL cholesterol significantly lower in the coronary heart disease group than in the remaining group. These results show that hyperlipoproteinemia and a decrease in HDL, together with other risk factors such as hypertension and anemia, play an important role in the accelerated development of atherosclerosis in a hemodialysis group.

Age Factors↗

[Increased cardiovascular arteriosclerosis risk in patients with analgesic nephropathy (author's transl)].

The retrospective investigation of 54 patients with analgesic nephropathy showed the relatively early occurrence of coronary sclerosis and an increased frequency of arteriosclerotic renal artery stenosis. Angina pectoris was found in 14 patients with a mean age of 48 1/2 years. Summation of risk factors is the probable cause of the tendency for arteriosclerosis: hypercholesterolaemia and hypertriglyceridaemia was found in 29 patients, arterial hypertension in 42 patients, which was so severe in half of the patients that combined treatment with two or more drugs was necessary. The causes of lipid metabolism disturbances as well as the pathogenesis of arterial hypertension are not known. Arteriosclerotic renal artery stenoses observed in 8 patients are not likely to be the cause of hypertension.

Adult↗

[Results of renal transplantation 1968-1979 (author's transl)].

173 renal transplantations were done over a period of 12 years. Among these were 162 first, 10 second and one third transplantation. The one year survival rate of transplanted kidneys (all cases) was around 50%, patient survival was 81.6%. Survival rates did not depend statistically on tissue compatibility, immediate function of kidney, duration of kidney conservation, donor age, commencement of graft versus host reaction, and duration of preoperative dialysis. Although the number of HLA identity has increased during the observation period, there was no increase of transplant survival rate. This may possibly be explained by the negative influence of the steady increase of conservation time during the same period.

Adolescent↗

[The clinical picture of panateritis nodosa].

The clinical picture of the panarteritis nodosa is characterized by vague early symptoms, manifestations in various organs and a changing prognosis. In seven patients with histologically proven panarteritis nodosa the clinical course was followed up over a long period. The commonest early symptoms were fever of unknown origin and a considerable loss of weight. Three out of seven patients showed in the initial phase a hypertension, in two other patients the blood pressure rose as the disease progressed. Those patients, whose renal function was impaired when the diagnosis was established, had a poor prognosis in spite of immunosuppressive therapy and dialysis. The life expectancy of these patients was between two and 16 months (in average 6,4 months). On the other side the clinical course in two patients without renal failure was more favourable; they are alive eight months and 15 years respectively after the diagnosis was confirmed.

Cerebral Hemorrhage↗

[Patients on dialysis--late fundus controls (author's transl)].

In 102 patients on dialysis for renal failure late fundus controls have been done to studie the response of retinal vessels to blood pressure reduction. In 52 patients follow up studies were possible. Only 4 patients showed reversible changes of the vessels, in 4 other patients changes increased. In the majority of the patients hypertensive vascular changes (stage I or II) remained unchanged. Young age and deep diastolic pressure seems to be necessary for normalization of the fundus vessels. Vessel changes did not improve if the diastolic pressure was 90--100 mmHg and more.

Adult↗

Investigations on latent erythropoietin (ESF) deficiency in non anemic patients with chronic renal disease using hypoxic stimulation methods.

So far the question has not been elucidated whether latent ESF-deficiency exists in patients with chronic renal disease during initial development of renal anemia. Therefore, ESF was determined in urine and serum of non anemic patients being exposed to acute hypoxia: 8 healthy volunteers and 8 patients who had a Ccreat below 48 ml/min were studied while in a hypobaric chamber for 4 subsequent periods of 10 h each (simulated maximal altitude 4000 m INA = 462 mm Hg). We also determined plasma iron turnover and reticulocyte counts. 10 h after the study began, the patients showed a significantly higher ESF-level than the normal volunteers. In the course of 48 h collection periods of urine under hypoxic conditions the mean ESF excretion in patients corresponded to 9.9 and in healthy persons to 7.3 Units. With regard to plasma iron turnover and reticulocyte count an increase was shown, but no significant differences existed between the two groups. A latent ESF-deficiency as the initial cause of renal anemia does not exist.

Adult↗

[Corneal changes in patients on dialysis for renal failure (author's transl)].

The corneas of 100 patients on dialysis for renal failure were observed. In 52 patients follow up studies were possible. 55 patients demonstrated limbal changes. On slit lamp biomicroscopy these changes showed to be similar to the white limbus girdle described by Vogt. Small limbal biopsies from five patients on dialysis were studies histopathologically and compared to biopsies from three patients with normal renal function. Only patients on dialysis showed senile elastosis and three of them epithelial and subepithelial hyaline deposits. Calcium deposition was the same in both groups.

Adolescent↗

Reversible encephalopathy following cephacetril therapy in high doses in a patient on chronic intermittent hemodialysis.

A patient on chronic intermittent hemodialysis at home showed signs of acute encephalopathy after an 8-day's treatment with a total dose of 78 g cephacetril (Celospor). Features included papilledema, loss of visual fields, severe generalized EEG changes and bilateral occipital abnormalities on a brain scintigram. Psychopathological findings consisted of a severe psychosis. The visual fields defects were the last sign of the encephalopathy to disappear.

Abscess↗

Investigations on pituitary and Leydig cell function in chronic hemodialysis and after renal transplantation.

The hypothalamus-pituitary-Leydig cell axis was investigated in 20 male patients undergoing intermittent hemodialysis and in 21 male patients following renal transplantation compared to normal controls. Plasma testosterone as well as luteinizing hormone and follicle stimulating hormone were determined by radioimmunoassay under basal conditions and after stimulation with choriongonadotropic hormone and hypothalamus releasing hormone respectively. Suppressed Leydig cell function has been demonstrated in dialysed patients as well as in patients after renal transplantation. The Leydig cell insufficiency is more pronounced in the hemodialysed patients. None of these showed testosterone levels in the normal range. They are different in various dialysis schedules. In contrast Leydig cell function is much better in patients after renal transplantation compared to those undergoing intermittent hemodialysis. But even after renal transplantation a diminished Leydig cell function takes place. The degree of Leydig cell insufficiency however varies individually. In a few cases Leydig cell function is restored completely after transplantation. It remains uncertain whether the duration of the posttransplantation period or the function of the graft effects Leydig cell function. Anterior lobe insufficiency has been excluded since plasma concentrations of gonadotropins were slightly elevated before and after LH-RH stimulation as compared to normals.

Adult↗